tbuckley/cabot-search huggingface dataset:
Risk of death among lung cancer patients before and during the COVID-19 pandemic.
Authors: Teddy Tai Loy Lee, Danyang Zheng, Sichao Wang, Abraham Ka Chung Wai, Feng-Ming Spring Kong
Journal: Journal of Clinical Oncology (2023)

10625 Background: The survival of lung cancer patients in Hong Kong before and during the COVID-19 pandemic is poorly understood. Methods: Patients diagnosed with lung cancer from January 1 2010 to October 31 2022 were recruited from all 43 public hospitals in Hong Kong. Patients who died on the day of cancer diagnosis were excluded. Patients between 2020-2022 (pandemic) were matched with patients diagnosed between 2010-2019 (pre-pandemic) using 1:1 propensity score matching, based on demographics and comorbidities such as age, sex, and Charlson Comorbidity Index (CCI), to study survival before and during the pandemic. The outcomes were 1-year and 6-month all-cause mortality. In subgroup analysis, patients were categorized into 12 groups, from 2010 to 2022, based on the year of first diagnosis of lung cancer to investigate yearly changes in mortality. Patients with confirmed diagnosis of COVID-19 infection were also analyzed. Results: A total of 42102 lung cancer patients (66.0% male, age 72±12 years (median±SD), CCI 7.00±2.42) were recruited from 2010 to 2021 with 1-year follow up. Only 36 patients were confirmed COVID-19 positive. The matched cohort consisted of 4958 pandemic patients (68.6% male, age 72±12 years, CCI 8.00±2.43) and 4958 pre-pandemic patients (67.7% male, age 73±12 years, CCI 7.53±2.48). 2782 (56.1%) and 3846 (77.6%) pandemic patients died within 6 months and 1 year respectively, compared to 2338 (47.2%) and 3194 (64.4%) pre-pandemic patients. In subgroup analysis by year of lung cancer diagnosis, patients diagnosed in 2021 had highest risk of 1-year mortality (85.1%). There was no significant difference in mortality between patients with and without confirmed COVID-19 positivity. The cohort of 2022 lung cancer patients, with higher COVID-19 positivity, was still undergoing follow-up and will be included in the analysis at the time of presentation. Conclusions: Lung patients diagnosed during the COVID-19 pandemic are associated with higher risk of death within the first year compared to that of pre-pandemic patients, and is likely not associated with COVID-19 positivity. [Table: see text]
Safety and feasibility of the addition of a radiosensitizing methionine-restricted diet to radiation therapy.
Authors: Malcolm David Mattes, Calvin N. Leung, Igor Koturbash, Sijin Wen, Geraldine M. Jacobson
Journal: Journal of Clinical Oncology (2023)

e15087 Background: Methionine is an amino acid necessary for cell growth and survival. Normal cells can tolerate methionine deficiency, but most cancer cells are methionine auxotrophs, requiring dietary intake since they cannot synthesize it. In vitro, methionine deficiency causes cancer cells to undergo cell cycle arrest and cell death, and in vivo a methionine restricted diet (MRD) enhances radiosensitization without significant adverse effects. Combining a MRD and radiation therapy (RT) for human malignancies has never been evaluated. The hypothesis of this Phase I study was that a MRD would be safe, and feasible to administer concurrently with curative-intent RT. Methods: Eligible patients included adults with any non-skin cancer malignancy undergoing standard RT without concurrent cytotoxic chemotherapy. The MRD consisted of low-protein cereals, grains, and breads; fruits; vegetables; margarines and oils; and simple carbohydrates. A clinical dietician developed a personalized meal plan with each subject to reduce methionine consumption to 5-10 mg/kg body weight/day, while maintaining adequate protein and caloric intake. An unlimited supply of a commercially available methionine-free protein supplement was provided to minimize hunger and weight loss. The MRD extended from 2 weeks before initiation of RT, through 2 weeks beyond completion of RT. The primary endpoint for safety was the rate of grade 3 or higher acute and late toxicities per CTCAE, over 12 months follow-up. Feasibility was assessed with a biweekly quantitative plasma amino acid panel during the MRD. The target accrual was 15 subjects. Results: Over two years, 53 patients were offered enrollment, 9 subjects enrolled, 5 completed the MRD and RT, and 4 withdrew during the MRD. The table summarizes subjects’ characteristics and outcomes. There was no grade 3 or higher adverse events attributable to the MRD. Methionine plasma levels varied over the course of treatment, and while no subject achieved the target of 13 μM, two nadired at 14 μM. The trial was closed early due to slow accrual and subjects’ difficulty maintaining the diet. Clinical trial information: NCT03574194 .Conclusions: This study suggests a MRD is safe with thoracic or abdominopelvic RT, with toxicities comparable to those expected with RT alone. However, the diet was challenging, and unacceptable to most patients with cancer. [Table: see text]
Response to programmed cell death protein 1 antibody in patients with Epstein-Barr virus-associated biliary tract cancer.
Authors: Wen-Zhuo He, Han-Bin Lin, Gui-Fang Guo, Liang-Ping Xia
Journal: Journal of Clinical Oncology (2023)

4071 Background: Epstein-Barr virus-associated biliary tract cancer (EBVaBTC) has a distinct genomic landscape and increased infiltration of CD3 + and CD8 + T cells. However, the efficacy of immunotherapy in EBVaBTC remains largely unknown. The aim of this study is to assess the efficacy of programmed cell death protein 1 (PD-1) antibody in EBVaBTC. Methods: Consecutive patients with metastatic biliary tract cancer diagnosed at our institution from January 2017 to December 2021 were identified. In situ hybridization was performed to detect EBV. The objective response to PD-1 antibody was assessed. We also analyzed the immune microenvironment of EBVaBTC by multiplex immunofluorescence staining, and performed the proteomic characterization of EBVaBTC. Results: A total of 131 patients with BTC who received PD-1 antibody were identified, of which 9 (6.9%) had EBVaBTC. All EBVaBTC cases were intrahepatic cholangiocarcinoma. EBVaBTC was not associated with deficient mismatch repair but with lymphoepithelioma-like carcinoma and hepatitis B virus infection. Four (44.4%) patients achieved a partial response, and the remaining five (55.6%) patients had stable disease. The response lasted for at least 12 months in 8 (88.9%) patients with EBVaBTC, including 4 patients received PD-1 antibody monotherapy. Blood EBV-DNA was detectable in all 9 patients (100%) with EBVaBTC. Multiplex immunofluorescence staining revealed more abundant CD3 + and CD8 + T cells infiltration in EBVaBTC than that of mismatch repair deficient BTC. A total of 8,379 proteins were identified by proteomics. Comparison of EBVaBTC and paired normal tissue revealed 547 differentially expressed proteins. Enrichment analysis demonstrated that differentially expressed proteins in the EBVaBTC were associated with EBV infection and T cell activation. We also observed the expression of immune checkpoint other than PD-1, including LAG-3 and TIM-3. Conclusions: Identification of EBVaBTC may represent a subset of patients with promising response to immunotherapy. [Table: see text]
Evaluating interventions to increase the uptake of NCCN genetic counseling recommendations.
Authors: Sophie Stempel, Shirlene Paul, Chelsea McPeek, Mia Alyce Levy, Rosalinda Alvarado
Journal: Journal of Clinical Oncology (2023)

10599 Background: Genetic counseling for hereditary breast cancer remains underutilized despite increased access. The lack of identification and/or referral of high-risk women for genetic counseling is the major contributor to the poor uptake. A cancer risk assessment program (CRA) utilizing NCCN guidelines was implemented in our breast imaging department to identify women at increased risk for breast cancer. We analyzed the impact of informing all women who get a screening mammogram of their genetic mutation risk and the effect of nurse navigation on increasing the subsequent uptake of genetic counseling. Methods: To assess the effectiveness of these interventions, data from July 2021 to January 2022 was extracted from the EMR and grouped into cohorts based on nurse navigation contact and the completion of genetic counseling. A chi-squared analysis was performed to determine the significance of the results. Results: A total of 22,915 patients participated in the CRA program during the study period. 2,671 (11.7%) patients qualified for genetic counseling based on NCCN guidelines. 414 (15.5%) of these patients completed a genetic counseling appointment. 298 of these patients received genetic testing (72%) and 18 (4.3%) had a pathogenic mutation found. The nurse navigator was able to reach 1,288 (48%) of the 2,671 patients (Cohort A). Of these patients, 324 (25.2%) completed genetic counseling appointments compared to 90 of the 1,383 (6.5%) patients who were not contacted by the nurse navigator (Cohort B). Statistical analysis determined there was a significant difference in uptake of genetic counseling between Cohort A and Cohort B (p&lt;.0001). Conclusions: The implementation of the CRA program at the breast imaging center uncovered many patients who qualified for genetic counseling and testing based on NCCN guidelines. Genetic counseling uptake is significantly increased in patients who are reached by a Nurse Navigator. These interventions allowed for the discovery of unsuspected deleterious genetic mutations which require more aggressive screening to allow for the early detection of breast cancer and better overall prognosis. [Table: see text]
Analysis of cell-free DNA (cfDNA) fragmentomes and prediction scores across distinct molecular subtypes.
Authors: Milou Schuurbiers, Alessandro Leal, Delasa Aghamirzaie, Bryan Chesnick, Erica Peters, Tony Wu, Debbie Jakubowski, Jennifer Tom, Nicholas C. Dracopoli, Peter B. Bach, Robert B. Scharpf, Victor E. Velculescu, Kim Monkhorst, Daan van den Broek, Michel van den Heuvel
Journal: Journal of Clinical Oncology (2023)

e15029 Background: Liquid biopsies have the advantage of being convenient in collecting tumor-derived DNA for clinical use. Genome-wide analysis of cell-free DNA (cfDNA) fragmentomes has emerged as a promising approach to detect lung cancer based on the examination of sequencing features other than actionable mutations. Here we report initial analyses of the DELFI (DNA evaluation of fragments for early interception) technology in patients enrolled in the Dutch Lung Cancer Early Molecular Assessment (LEMA) trial (NCT02894853), a prospective, observational, and multicenter study, to evaluate fragmentation patterns in genotyped blood samples with actionable alterations irrespective of disease stage and histology subtype. Methods: Plasma samples from 576 patients with an established diagnosis of lung cancer but awaiting the start of definitive treatment were processed and examined using low-coverage whole-genome sequencing. A lasso model that incorporated genome-wide fragmentation profiles was trained on an internal Delfi Diagnostics cohort and used to generate patient-specific DELFI scores for participants in LEMA. Results: Enrollees comprised 531 individuals with non-small cell lung cancer, 38 with small-cell lung cancer, and 7 with unknown lung cancer type. Most patients were diagnosed with late-stage disease (28% stage I, 10% stage II, 26% stage III, and 36% stage IV). Current smokers (N = 238; 41%) and former smokers (N = 295, 51%) outnumbered never smokers (N = 43; 8%). Analysis showed a stepwise increase of the DELFI scores from T1 to T4 and N0 to N1-3 disease, associating aberrant fragmentation profiles with the overall tumor burden. Small-cell carcinomas and squamous cell carcinomas presented with higher DELFI scores than adenocarcinomas ( p&lt; 1e-7, generalized linear model). Patients without a smoking history had similar scores to those who had a previous history of smoking. When adjusted for stage, mutation status in ALK, BRAF, EGFR, ERBB2, KRAS, MET, RET, and ROS were not associated with DELFI scores ( p= 0.5, likelihood ratio test). Similarly, PD-L1 staining did not significantly affect DELFI scores when a 1% cutoff was applied to cases with PD-L1 staining data ( p= 0.07, generalized linear model). Conclusions: Our results reveal that DELFI scores increase stepwise with stage and are higher in small-cell and squamous cell carcinomas. The LEMA study reinforces the potential usefulness of genome-wide cfDNA fragmentation profiling as a liquid biopsy approach for identifying patients with lung cancer regardless of smoking status, somatic driver mutation, and PD-L1 expression scores.
Prognostic and predictive implications of plasma ctDNA in guiding first-line targeted therapy for metastatic <i>HER2</i>-mutant non-small cell lung cancer (NSCLC).
Authors: Si-Yang Liu, Justin Jee, Fernando Costa Santini, Adam Jacob Schoenfeld, Jordan Eichholz, Kaylie Johnson, Andres Martinez, Jiannan Guo, Nadeem Riaz, Nancy Y. Lee, Luke Roy George Pike, Howard I. Scher, Alexander E. Drilon, Maria E. Arcila, Jorge S. Reis-Filho, Pedram Razavi, David Randolph Jones, Charles M. Rudin, James M. Isbell, Bob T. Li
Journal: Journal of Clinical Oncology (2023)

9052 Background: Trastuzumab deruxtecan (T-DXd) is the first HER2-targeted drug approved for NSCLC with human epidermal growth factor receptor 2 ( HER2, ERBB2) mutation in the second or later line settings. However, the optimal first-line treatment for these patients remains unclear. Access to rapid tissue sequencing is not always available, thus presenting challenges to first-line drug development. Circulating tumor DNA (ctDNA) analysis has the potential to overcome these obstacles to guide optimal first-line targeted therapy for patients with HER2-mutant NSCLC. Methods: We retrospectively analyzed patients with metastatic HER2-mutant NSCLC who underwent prospective clinical ctDNA sequencing at Memorial Sloan Kettering Cancer Center (MSK) from January 2016 to September 2022. HER2 mutations were identified by next-generation sequencing through MSK-IMPACT, MSK-ACCESS or Resolution ctDx Lung. Results: We identified 64 patients with metastatic HER2-mutant NSCLC who had received at least one line of systematic therapy. The median age was 63 years (range: 23–90), and there were more women (n = 38, 60%), and never-smokers (n = 38, 60%). The activating HER2 mutations included exon 20 insertions (73%), exon 8 (11%), 19 (11%), and 20 SNVs (5%). Plasma ctDNA was tested before initial therapy in 40 patients with a median overall survival (OS) of 28 months (95% CI 21-34), in whom 31 patients (78%) had at least one detectable ctDNA alteration by MSK-ACCESS and ctDx Lung. 55% (17/31) received chemoimmunotherapy with pembrolizumab as the first-line treatment. The median time to treatment discontinuation (TTD) was 6 months (95%CI 5.5-6.9). Additionally, 19% of patients (6/31) received a HER2-targeted antibody-drug conjugates (ADC) as first-line treatment with a median TTD of 6 months (95% CI 2-10), including 5 with T-DM1 and one who received first-line T-DXd treatment with a TTD of 9 months. Patients with baseline ctDNA alterations had significantly shorter OS (hazard ratio (HR), 5.25; 95% CI, 1–24; p = 0.019). Conclusions: Baseline plasma ctDNA has the potential to guide first-line targeted therapy for patients with HER2-mutant NSCLC. As an independent negative prognostic biomarker, detectable ctDNA at baseline would need to be taken into account for patient selection in future studies to avoid underestimating the effects of therapy.
Hyperthermic intraperitoneal chemotherapy in platinum-sensitive relapsed epithelial ovarian cancer: The CHIPOR randomized phase III trial.
Authors: Jean-Marc Classe, Pierre Meeus, Eric Leblanc, Romuald Wernert, Francois Quenet, Frédéric Marchal, Gilles Houvenaeghel, Anne-Sophie Bats, Gwenael Ferron, Cecile Brigand, Dominique Berton, Laurence Gladieff, Florence Joly, Isabelle Laure Ray-Coquard, Sylvaine Durand-Fontanier, Gabriel Liberale, Emilie Brument, Bernard Asselain, Loic Campion, Olivier Glehen
Journal: Journal of Clinical Oncology (2023)

5510 Background: Standard treatment for patients with first platinum-sensitive relapse of epithelial ovarian cancer (EOC) is based on surgery and second-line systemic chemotherapy (CT). The role of hyperthermic intra-peritoneal chemotherapy (HIPEC) remains uncertain. Methods: The CHIPOR multicentric randomized phase III trial (NCT01376752), conducted in 31 institutions, enrolled patients with a first platinum-sensitive relapse (platinum-free interval of ≥6 months) of EOC. Patients were treated with 6 cycles of platinum and taxane based CT ± bevacizumab, and those amenable to a complete cytoreductive surgery at the end of CT were enrolled and randomly assigned to receive HIPEC (cisplatin 75 mg/m² at 41°C for 60 min) or not. Randomization was performed during complete cytoreductive surgery, stratified by center, surgical outcome (no residual disease vs residual &lt;0.25 cm), chemotherapy-free interval before relapse, and PARP inhibitor use (yes vs no). The primary endpoint was overall survival (OS). The target sample size was 404 evaluable patients, providing 80% power at 5% alpha after 268 deaths. Secondary endpoints included progression-free survival (PFS), peritoneal PFS, patient-reported outcomes, safety, and postoperative morbidity and mortality (≤60 days after surgery). Results: Between May 11, 2011, and May 14, 2021, 415 patients were randomized. Baseline characteristics were balanced between treatment arms. At the data cutoff (Jan 8, 2023), with a median follow-up of 6.2 years, 268 patients (65%) had died. Efficacy results are summarized below. Conclusions: HIPEC significantly improves OS and peritoneal PFS of women with first platinum-sensitive relapse of EOC treated with second-line platinum-based CT followed by secondary complete cytoreductive surgery. Ongoing analyses, including patient reported outcome, BRCA status, bevacizumab exposure, and subsequent therapy, will be presented. Clinical trial information: NCT01376752 . [Table: see text]
30-day readmissions for venous thromboembolism and pulmonary embolism in patients with pancreatic cancer: A national population-based study.
Authors: Ted Akhiwu, Philip Onyekaoso Kanemo, Ayobami Gbenga Olafimihan, Muhammad Bilal Ibrahim, Anthonia Ijeli, Ehizogie Edigin
Journal: Journal of Clinical Oncology (2023)

e16318 Background: Pancreatic cancer patients have a strong risk of Deep Venous thrombosis (DVT). Pulmonary Embolism (PE) can be a fatal complication of DVT. Both DVT/PE increases the risk of hospitalization and subsequent readmission. National population-based studies are scarce on DVT/PE readmissions among pancreatic cancer patients in the United States (U.S). In this study, we aim to describe the rate, reasons for readmissions, and outcome of readmissions for pancreatic cancer patients hospitalized for DVT/PE in the U.S. Methods: We analyzed the 2018 Nationwide Readmissions Database (NRD). It includes nested and weighted discharge data for 60% of the total U.S population from 28 states. These data are stratified in clusters to produce national estimates. The NRD captures admissions on a calendar-year basis without links to the following or preceding year. We included index hospitalizations for all pancreatic cancer patients (aged ≥18 years) admitted principally for DVT/PE using the International Classification of Diseases (ICD)-10 codes. We excluded elective and traumatic readmissions. 30-day readmission was calculated as the percentage of patients readmitted within 30 days over index hospitalizations that were discharged alive. Using a "rank" command in STATA, the most common reasons for readmission were outlined. Logistic regression was used to compare inpatient mortality between readmissions and index hospitalizations. STATA, 16 was used for analysis. Since NRD contains de-identified patient data, Institutional Review Board (IRB) review was not sought. Results: A total of 2339 index hospitalizations for DVT/PE among pancreatic cancer patients were discharged alive. Among these, 510 (21.8%) were readmitted within 30 days. The top 5 reasons for 30-day readmissions were sepsis, pancreatic cancer, PE without cor pulmonale, metastatic cancer of the liver and intra-hepatic duct, and pneumonia. 30-day readmissions were responsible for an aggregate of 5.9 million U.S dollars in hospital costs and 2443 hospital days in 2018. Compared to index hospitalizations, 30-day readmissions had higher inpatient mortality (13.4% vs 5.9%, p &lt; 0.0001). Conclusions: 30-day readmissions for DVT/PE in patients with pancreatic cancer have a significant healthcare economic burden. PE, Pancreatic cancer, and infections were common reasons for readmissions. Readmissions have significantly greater inpatient mortality compared to index admissions. Adequate management of DVT/PE and underlying malignancy during index admissions and ensuring timely outpatient follow-up are important in reducing 30-day readmissions of these patients.
In-hospital outcomes of patients with pancreatic cancer and venous thromboembolism.
Authors: Ankushi Sanghvi, Dhairya Nanavaty, Kannu Bansal, Anuroop Yekula, Gayatri Narayan, Fnu Janamejey, Shailja Shah
Journal: Journal of Clinical Oncology (2023)

e16317 Background: Pancreatic cancer accounts for about 3.2% of all new cancers in the US. It has dismal 5-year relative survival of 11.5% and accounts for 8.2% of all cancer deaths. Studies have shown a strong association of pancreatic cancer with venous thromboembolism (VTE). However, data surrounding outcomes associated with VTE in this population is limited. We aim to estimate the effect of VTE on mortality and healthcare utilization in this population. Methods: We queried the National Inpatient Sample (NIS) 2017-2019 for all adult patients with a diagnosis of pancreatic cancer. The cohort was further classified by the presence of VTE (either acute deep vein thrombosis (DVT) or acute pulmonary embolism (PE)). The primary outcome of interest was in-hospital mortality, and secondary outcomes included hospitalization cost and length of stay, reflecting resource utilization. Multivariable regression analysis was performed to examine the association. Results: Over a period of 3 years, 392,744 admissions were identified with a diagnosis of pancreatic cancer. The mean age was 67 years, and 48% were females. The prevalence of acute DVT and acute PE was 5.0% and 5.8% respectively. In-hospital mortality was roughly 12% in the study cohort who had either DVT or PE. The odds of all-cause mortality were higher in pancreatic cancer admissions complicated by DVT (OR 1.59, 95% CI: 1.34-1.70, p&lt;0.001) or PE (OR 1.39, 95 %CI: 1.23-1.58, p&lt;0.001). The presence of VTE was also associated with higher hospital costs ($17,351 (14,256-20,446, p&lt;0.001) for DVT, and $5,710 (2,679-8,740, p&lt;0.001) for PE and longer hospital stay (7.2 vs 5.7, p&lt;0.001) for DVT and (6.6 vs 5.7, p&lt;0.001) for PE. Conclusions: Our study suggests that the presence of VTE portends poor outcomes in patients with pancreatic cancer. They also increase healthcare expenditure and lead to a longer hospital stay. Current guidelines (2020) recommend against offering thromboprophylaxis to patients with any cancer. Given the worse outcomes, this study reflects the need to formulate risk assessment models for the role of primary thromboprophylaxis in pancreatic cancer.